Objective: To characterise cardiac remodelling, exercise capacity and fibroinflammatory biomarkers in patients with aortic stenosis (AS) with and without diabetes, and assess the impact of diabetes on outcomes. Methods: Patients with moderate or severe AS with and without diabetes underwent echocardiography, stress cardiovascular magnetic resonance (CMR), cardiopulmonary exercise testing and plasma biomarker analysis. Primary endpoint for survival analysis was a composite of cardiovascular mortality, myocardial infarction, hospitalisation with heart failure, syncope or arrhythmia. Secondary endpoint was all-cause death. Results: Diabetes (n=56) and non-diabetes groups (n=198) were well matched for age, sex, ethnicity, blood pressure and severity of AS. The diabetes group had higher body mass index, lower estimated glomerular filtration rate and higher rates of hypertension, hyperlipidaemia and symptoms of AS. Biventricular volumes and systolic function were similar, but the diabetes group had higher extracellular volume fraction (25.9%±3.1% vs 24.8%±2.4%, p=0.020), lower myocardial perfusion reserve (2.02±0.75 vs 2.34±0.68, p=0.046) and lower percentage predicted peak oxygen consumption (68%±21% vs 77%±17%, p=0.002) compared with the non-diabetes group. Higher levels of renin (log₁₀renin: 3.27±0.59 vs 2.82±0.69 pg/mL, p<0.001) were found in diabetes. Multivariable Cox regression analysis showed diabetes was not associated with cardiovascular outcomes, but was independently associated with all-cause mortality (HR 2.04, 95% CI 1.05 to 4.00; p=0.037). Conclusions: In patients with moderate-to-severe AS, diabetes is associated with reduced exercise capacity, increased diffuse myocardial fibrosis and microvascular dysfunction, but not cardiovascular events despite a small increase in mortality.

Objectives To explore the ethnic differences in patients undergoing aortic valve (AV) intervention for severe aortic stenosis (AS) in Leicestershire, UK. Methods Retrospective cohort study of all surgical aortic valve replacement (SAVR) and transcatheter aortic valve implantation (TAVI) at a single tertiary centre between April 2017 and March 2022, using local registry data. Results Of the 1231 SAVR and 815 TAVI performed, 6.5% and 3.7% were in ethnic minority patients, respectively. Based on the 2011 Census data for those with a Leicestershire postcode, crude cumulative rate of SAVR (n=489) was 0.64 per 1000 population overall and 0.69, 0.46 and 0.36 in White, Asian and Black populations, respectively; and 0.50 per 1000 population overall for TAVI (n=383), with 0.59, 0.16 and 0.06 for White, Asian and Black populations, respectively. Asians undergoing SAVR and TAVI were 5 and 3 years younger, respectively, than white patients with more comorbidities and a worse functional status. The age-adjusted cumulative rates for SAVR were 0.62 vs 0.72 per 1000 population for White and Asian patients and 0.51 vs 0.39 for TAVI. Asians were less likely to undergo SAVR and TAVI than White patients, with a risk ratio (RR) of 0.66 (0.50–0.87) and 0.27 (0.18–0.43), respectively, but the age-adjusted RR was not statistically significant. Conclusion The crude rates of AV interventions are lower in Asian patients compared with the White population in Leicestershire, although age-adjusted rates were not statistically different. Further research to determine the sociodemographic differences in prevalence, incidence, mechanisms and treatment of AS across the UK is required.

Background: Health inequalities in cardiovascular care have been identified in the UK. The sociodemographic characteristics of patients undergoing intervention for aortic stenosis (AS) in England, and the impact of COVID-19, is unknown. Methods: National linked data sets identified all surgical aortic valve replacement (SAVR) and transcatheter aortic valve implantation (TAVI) for AS, and post-intervention cardiovascular mortality, between 2000 and 2023. Results: Of 179 645 procedures, there were 139 990 SAVR (mean age 71±10.8 years, 64% male, 96.0% white) and 39 655 TAVI (mean age 81±7.7 years, 57% male, 95.7% white). Rates of SAVR declined during COVID-19 for all groups, but TAVI rates increased steadily. Women were older; ethnic minority groups and those from most deprived areas were younger, with greater comorbidities. Women and more deprived groups had lower rates of SAVR (age-standardised rates per 100 000 in 2020–2023: 17.07 vs 6.65 for men vs women; 9.82 vs 10.10 for Index of Multiple Deprivation (IMD)-1 vs IMD-5) and TAVI (20.20 vs 9.79 for men vs women; 9.55 vs 13.36 for IMD-1 vs IMD-5). These discrepancies widened over time. Ethnic differences were observed for SAVR, with the lowest rates in black patients. Cardiovascular mortality post-intervention was lower in female patients and with decreasing deprivation, with no ethnicity-based differences. Conclusions: There are differences in intervention rates for AS in England, with lower rates in female patients and to a lesser extent, those from the most deprived areas and ethnic minority groups. These variations have widened over time. Post-intervention cardiovascular mortality is lower in women and with decreasing deprivation. Public health measures and research are needed to identify the true prevalence of AS in different populations, and the reasons for potential inequalities.

Background: Previous studies have suggested an adverse role of epicardial adipose tissue (EAT) in aortic stenosis (AS), potentially mediated by direct effects on the myocardium. This study aimed to assess whether EAT volume and density are associated with cardiac remodelling and clinical outcomes in a well-phenotyped cohort of patients with initially asymptomatic AS. Methods: In this post hoc exploratory analysis of a multicentre, prospective longitudinal study, asymptomatic patients with moderate-to-severe AS (n=136; age 68.6 (60.1, 75.3) years, 27% female) and control participants (n=39; age 59.0 (54.0, 67.0) years, 38% female) underwent echocardiography, cardiac CT and MRI. EAT volume and mean CT attenuation were measured from non-contrast cardiac CT using an automated deep learning software. The primary outcome was symptoms necessitating valve replacement, cardiovascular death or major adverse cardiac event. Results: Participants with AS had significantly higher indexed EAT volumes (56.5 vs 38.8 cm ³ /m ² , p<0.001) and lower EAT attenuation (−76.3 vs −69.9 Hounsfield units, p<0.001). Both measures were correlated with markers of AS severity. Indexed EAT volume was not associated with cardiac remodelling in AS after correcting for confounding variables; however, a higher mean EAT CT attenuation was associated with higher indexed left ventricular mass. There were 42 (31%) primary outcome events over a median of 370 days. Lower indexed EAT volume and higher mean CT attenuation were associated with the outcome, independent of age and sex. Indexed EAT volume remained negatively associated after further adjustment for AS severity. Conclusion: Indexed EAT volume was higher in patients with AS, but not associated with MRI markers of cardiac remodelling. A higher indexed EAT volume was independently associated with a lower occurrence of symptoms and cardiovascular events. Further studies are needed to corroborate these findings and whether EAT has a potentially protective role in symptom progression in AS. Trial registration numbers: NCT03518645 , NCT03132129 .

Background: Coronary microvascular disease is associated with adverse prognosis in a range of cardiovascular diseases, but its prognostic role in patients with aortic stenosis (AS) is unclear. The aim of this systematic review and meta-analysis is to determine the prognostic role of myocardial perfusion and coronary flow reserve, assessed using non-invasive imaging modalities, in patients with AS. Methods: We conducted a systematic review and meta-analysis of all studies assessing myocardial perfusion reserve (MPR) or coronary flow reserve (CFR) in patients with AS and reporting clinical outcomes, from inception to January 2024. The definition of abnormal MPR/CFR and major adverse cardiovascular events (MACE) was that used in each study. Estimates of effect were calculated from hazard ratios (HRs) and 95% confidence intervals (CIs) using a random-effects model. Results: Four studies comprising 384 participants met the inclusion criteria. Myocardial/coronary blood flow was assessed using Doppler echocardiography (n = 2), PET (n = 1), or cardiac magnetic resonance (n = 1). The median optimal cutoff for MPR/CFR across all studies was 2.01 (range 1.85–2.13), with 109 events. Impaired MPR/CFR was associated with a higher incidence of MACE (HR 3.67, 95% CI: 1.66, 8.09, I² = 63%) in the overall population. Conclusions: Reduced MPR/CFR is associated with increased risk of MACE in patients with AS, although significant heterogeneity exists in published studies. Further studies are required to establish its role in the risk stratification of asymptomatic patients with AS.

Aortic valve replacement (AVR) leads to reverse cardiac remodeling in patients with aortic stenosis (AS). The aim of this secondary pooled analysis was to assess the degree and determinants of changes in myocardial perfusion post AVR, and its link with exercise capacity, in patients with severe AS. A total of 68 patients underwent same-day echocardiography and cardiac magnetic resonance imaging with adenosine stress pre and 6–12 months post-AVR. Of these, 50 had matched perfusion data available (age 67 ± 8 years, 86% male, aortic valve peak velocity 4.38 ± 0.63 m/s, aortic valve area index 0.45 ± 0.13cm²/m²). A subgroup of 34 patients underwent a symptom-limited cardiopulmonary exercise test (CPET) to assess maximal exercise capacity (peak VO₂). Baseline and post-AVR parameters were compared and linear regression was used to determine associations between baseline variables and change in myocardial perfusion and exercise capacity. Following AVR, stress myocardial blood flow (MBF) increased from 1.56 ± 0.52 mL/min/g to 1.80 ± 0.62 mL/min/g (p < 0.001), with a corresponding 15% increase in myocardial perfusion reserve (MPR) (2.04 ± 0.57 to 2.34 ± 0.68; p = 0.004). Increasing severity of AS, presence of late gadolinium enhancement, lower baseline stress MBF and MPR were associated with a greater improvement in MPR post-AVR. On multivariable analysis low baseline MPR was independently associated with increased MPR post-AVR. There was no significant change in peak VO₂ post-AVR, but a significant increase in exercise duration. Change in MPR was associated with change in peak VO₂ post AVR (r = 0.346, p = 0.045). Those with the most impaired stress MBF and MPR at baseline demonstrate the greatest improvements in these parameters following AVR and the magnitude of change in MPR correlated with improvement in peak VO₂, the gold standard measure of aerobic exercise capacity.